Malakoplakia of allograft gastrointestinal tract including stomach, ileum, and colon and native colon.
The patient's antibiotic treatment was continued and she improved clinically; she was discharged home six weeks after admission. Due to deconditioning associated with her prolonged hospital stay as well as new-onset motor axonal neuropathy which may be due to her immunosuppressive medication, she required outpatient physical therapy.
The features of the generalized intestinal histiocytic infiltrate present throughout our patient's entire gastrointestinal allograft are diagnostic of malakoplakia. The characteristic intracytoplasmic inclusions (Michaelis-Gutmann bodies) were found to be ubiquitous in the later biopsies and in retrospect, rare MG bodies were found in the previous set of biopsies.
Malakoplakia is a rare inflammatory condition which usually affects bladder mucosa (Voight, 1958) but can also involve the gastrointestinal tract (Terner and Lattes, 1965) and other sites. It is characterized by soft, pale yellow plaques on the mucosa. Malakoplakia is thought to result from the insufficient killing of gram negative bacteria by macrophages. The partially digested bacteria accumulate in macrophages along with iron and calcium deposits. These basophilic, often targetoid, inclusions are called Michaelis-Gutmann (MG) bodies (Michaelis and Gutmann, 1902). Malakoplakia is usually found in patients with a history of immunosuppression due to lymphoma, another malignant neoplasm, or transplant, most commonly renal transplant, and is treated with antibiotics.
Malakoplakia most commonly occurs in the urogenital tract, but the second most common site is the gastrointestinal tract. Less common sites include skin (Arul and Emmerson, 1977), breast (DiLeo and Anastasi, 1969), lungs and skeleton (Gupta, Schuster, and Christian, 1972) and brain (Takei, 1971). Gastrointestinal malakoplakia usually occurs in the colon and rectum, but has been reported in the stomach, duodenum, and appendix (Sekaran 2011, Kim 2003). It can be asymptomatic or present with diarrhea, abdominal pain, hemorrhage, or obstruction; involvement can be patchy or diffuse, with plaques, polyps, or a large mass. Gastrointestinal malakoplakia can be associated with gastrointestinal neoplasm (McClure, 1981), systemic disease such as chronic granulomatous disease, ulcerative colitis, tuberculosis, AIDS and celiac disease, or solid organ transplant (Yousif 2006, Keitel 2012, Mcclure 1981, Dasgupta, 1999). Malakoplakia usually occurs in adults, but it has previously been reported in children from 6 wks to 12 years old (McClure, 1981, Sekaran 2011, Kajbafzadeh, 2004), who often have associated systemic disease such as hereditary immunodeficiency. Occasionally malakoplakia can occur in immunocompetent children and adults with no significant medical history (Borghesi, 1997, Sekaran 2011).
Most of the solid organ transplants in malakoplakia cases are renal (Bae, 2013, Berney, 1999, Shah 2010, Yousif 2006, Keitel 2012). Post-transplant malakoplakia can occur either in the transplanted organ (Keitel 2012) or native organs. Gastrointestinal malakoplakia has previously been reported in children (Divya, 2010, Sekaran 2011, Krauel 2009, Kini 2005).
Gastrointestinal malakoplakia can be associated with solid organ transplant, especially when complicated by recurrent E coli infections (Yousif 2006, Keitel 2012, Mcclure 1981). Of note, our patient was admitted for E coli sepsis. Because malakoplakia is associated with immunosuppression, it is noteworthy that our patient had recently received additional immunosuppressive therapy for an episode of acute cellular rejection two months prior to admission. Our patient was receiving tacrolimus therapy, and gastrointestinal malakoplakia presenting with chronic diarrhea in an adult liver transplant patient receiving tacrolimus has been previously reported (Kim, 2007). As in our case, microscopy in previous cases has shown macrophages containing Gram-negative bacilli (McClure, 1981).
The etiology of malakoplakia is still not known; hypotheses include defective lysosomes and abnormal microtubular assembly similar to Chediak Higashi (Dasgupta, 1999). Phagocytes cannot kill bacteria without degranulation of lysosomes, for which normal microtubules are essential. Cholinergic agents and vitamin C, which help with phagocytic function, are a possible therapeutic adjunct in malakoplakia. Interestingly, our patient received her allograft for microvillus inclusion disease, which is a genetic myosin abnormality that leads to a congenital lack of apical microvilli in the epithelial cells of the small intestine as well as endosomal and lysosomal abnormalities. Although lysosomal abnormalities may have predisposed her to malakoplakia, the disease was the most severe in the allograft, not native, parts of her gastrointestinal system.
Malakoplakia can be silent (Bae, 2013) or present with severe clinical symptoms including intestinal perforation, sepsis, multiple organ failure, and death in adults (Berney, 1999). Malakoplakia can present with pseudotumor mass effects as well (Yousif 2006, Berney 1999). Malakoplakia can resolve completely when treated with extended course antibiotics (Yousif 2006). Our pediatric patient was very fortunate to survive severe malakoplakia with few sequalae. Though rare, malakoplakia should be on the differential in a transplant patient with abdominal symptoms and histocytic infiltrates on biopsy.
Voight, J (1958) Malacoplakia of the urinary tract. Review of the literature. Report of two new cases. Acta pathologica et microbiologica scandinavica, 44, 377.
Terner Jy, Lattes R. Malakoplakia Of Colon And Retroperitoneum. Report Of A Case With A Histochemical Study Of The Michaelis-Gutman Inclusion Bodies. Am J Clin Pathol. 1965 Jul;44:20-31. PubMed PMID: 14314215.
Michaelis, L and Gutmann, D (1902) Ueber Einschlusse in Blasentumoren. Zeitschrift fur klinische Medizin, 47, 208. Arul and Emmerson, 197
Di Leo S, Anastasi M. [Is there malacoplakia of the breast? Apropos of an unusual evolution of puerperal mastitis]. Arch De Vecchi Anat Patol. 1969 Oct;55(2):303-18. Italian. PubMed PMID: 5404508.
Gupta RK, Schuster RA, Christian WD. Autopsy findings in a unique case of malacoplakia. A cytoimmunohistochemical study of Michaelis-Gutmann bodies. Arch Pathol. 1972 Jan;93(1):42-8. PubMed PMID: 4108495.Mirra, 1971
Takei Y, Mirra SS. Intracytoplasmic hyaline inclusion bodies in the nerve cells of the hypoglossal nucleus in human autopsy material. Acta Neuropathol.1971;17(1):14-23. PubMed PMID: 5100912.
Arul KJ, Emmerson RW. Malacoplakia of the skin. Clin Exp Dermatol. 1977 Jun;2(2):131-5. PubMed PMID: 884891.
Kim JB, Han DS, Lee HL, Park JY, Jeon YC, Sohn JH, Jang SJ, Park YW. Malacoplakia of the stomach: case report and review. Gastrointest Endosc. 2003 Sep;58(3):441-5. Review. PubMed PMID: 14528226.
Sekaran A, Dubale N, Lakhtakia S, Raju B, Ramchandani M, Darisetty S, Reddy DB, Reddy DN. Malakoplakia: an unusual cause of lower GI bleeding in a child. Gastrointest Endosc. 2011 Aug;74(2):443-5. doi: 10.1016/j.gie.2010.11.034. Epub 2011 Feb 2. PubMed PMID: 21288516.Kim 2003
McClure J. Malakoplakia of the gastrointestinal tract. Postgrad Med J. 1981. Feb;57(664):95-103. PubMed PMID: 7267514; PubMed Central PMCID: PMC2424798.
Yousif M, Abbas Z, Mubarak M. Rectal malakoplakia presenting as a mass and fistulous tract in a renal transplant patient. J Pak Med Assoc. 2006 Aug;56(8):383-5. PubMed PMID: 16967795.
Keitel E, Pêgas KL, do Nascimento Bittar AE, Dos Santos AF, da Cas Porto F, Cambruzzi E. Diffuse parenchymal form of malakoplakia in renal transplant recipient: a case report. Clin Nephrol. 2012 Nov 29. [Epub ahead of print] PubMed PMID: 23195831.
Dasgupta P, Womack C, Turner AG, Blackford HN. Malacoplakia: von Hansemann's disease. BJU Int. 1999 Sep;84(4):464-9. Review. PMID:10468763[PubMed - indexed for MEDLINE]
Kajbafzadeh A, Baharnoori M. Renal malakoplakia simulating neoplasm in a child: successful medical management. Urol J. 2004 Summer;1(3):218-20. PubMed PMID: 17914695.
Borghesi MR, Cogolo L, Mazzarello PL, Romanelli R. Malakoplakia of the appendix. Minerva Chir. 1997 Apr;52(4):465-7. Review. PubMed PMID: 9223896.
Bae GE, Yoon N, Park HY, Ha SY, Cho J, Lee Y, Kim KM, Park CK. Silent Colonic Malakoplakia in a Living-Donor Kidney Transplant Recipient Diagnosed during Annual Medical Examination. Korean J Pathol. 2013 Apr;47(2):163-6. doi:10.4132/KoreanJPathol.2013.47.2.163. Epub 2013 Apr 24. PubMed PMID: 23667376; PubMed Central PMCID: PMC3647129.
Berney T, Chautems R, Ciccarelli O, Latinne D, Pirson Y, Squifflet JP. Malakoplakia of the caecum in a kidney-transplant recipient: presentation as acute tumoral perforation and fatal outcome. Transpl Int. 1999;12(4):293-6. PubMed PMID: 10460878.
Shah MB, Sundararajan S, Crawford CV, Hartono C. Malakoplakia-induced diarrhea in a kidney transplant recipient. Transplantation. 2010 Aug 27;90(4):461-2. doi: 10.1097/TP.0b013e3181e7a387. PubMed PMID: 20720480.
Divya P, Crasta JA. Pediatric malakoplakia of colon: a report of two cases. Pediatr Surg Int. 2010 Mar;26(3):323-5. doi: 10.1007/s00383-010-2551-3. Epub 2010 Jan 26. PubMed PMID: 20101508.
Krauel L, García-Aparicio L, Pérez N, Laguna A, Camacho A, Vilar P, Rodó J, Ribó JM. Urinary and gastrointestinal malakoplakia in a 12-year-old girl. Urology. 2009 Jan;73(1):87-9. doi: 10.1016/j.urology.2008.05.043. Epub 2008 Oct 26. PubMed PMID: 18952264.
Kini U, Km S, Das K. Malakoplakia of the colon in an eight-year-old child. Diagn Cytopathol. 2005 Aug;33(2):145. PubMed PMID: 16007673.
Kim PT, Davis JE, Erb SR, Yoshida EM, Steinbrecher UP. Colonic malakoplakia in a liver transplant recipient. Can J Gastroenterol. 2007 Nov;21(11):753-5. PubMed PMID: 18026580; PubMed Central PMCID: PMC2658591.
Contributed by Martina Pejchal, MD, PhD and Jennifer Picarsic, MD